Postnatal Intermittent Hypoxia and Respiration: Potenti*

产后间歇性缺氧和呼吸：电位*

• 批准号: 6883771
• 负责人: STEPHEN R REEVES
• 金额: $ 2.57万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6883771
• 关键词: disease /therapy duration; early experience; enzyme activity; hypoxia; laboratory rat; long term potentiation; phrenic nerve; predoctoral investigator; protein kinase C; pulmonary respiration; respiratory disorder epidemiology; respiratory distress syndrome of newborn; sleep apnea; sudden infant death syndrome

DESCRIPTION (provided by applicant): Intermittent hypoxia (IH) is a frequent condition in clinical medicine (e.g., sleep apnea, SIDS), which bears substantial morbidity and mortality. Furthermore, organismal adaptations to IH suggest the formation of specific forms of neuronal plasticity. While substantial study of the effects of IH has been performed in the mature mammal, little if any work has been done during the early phases of post-natal development, a unique period of neuronal vulnerability and adaptation. Therefore, we hypothesized that post-natal intermittent hypoxia, such as occurs in sleep apnea, may impose long-term modifications in respiratory control, thereby leading to a form of metaplasticity of respiratory patterning. The latter modification of the respiratory network induced by early post-natal IH could impose either a functionally favorable or a maladaptive alteration of the respiratory response system. To examine this issue, we will: (i) characterize the effects of post-natal IH on normoxic ventilation and on hypoxic and hypercapnic ventilatory responses in freely behaving rats.; (ii) assess the effects of IH on phrenic motor nerve long-term facilitation (LTF).; (iii) determine the potential role of signaling pathways, particularly protein kinase C (PKC), in the long-term modification of ventilation imposed by IH through development. This work will therefore contribute to the understanding of potential mechanisms mediating not only early adaptations to IH but also provide insights to long-lasting changes in ventilation that may develop when a conditioning stimulus is applied during critical phase of maturation.

描述（由申请人提供）：间歇性缺氧（IH）是临床医学（例如睡眠呼吸暂停，SIDS）的常见状况，具有很大的发病率和死亡率。此外，对IH的生物适应表明了特定形式的神经元可塑性。尽管对成熟的哺乳动物进行了大量研究，但在产后发育的早期阶段，几乎没有做任何工作，这是一个独特的神经元脆弱性和适应性时期。因此，我们假设产后间歇性缺氧（例如在睡眠呼吸暂停中发生）可能会在呼吸控制中施加长期修饰，从而导致呼吸模式的替代性的形式。产后IH引起的呼吸网络的后期修饰可能会对呼吸反应系统进行功能良好或适应不良的改变。为了检查这个问题，我们将：（i）表征产后IH对自由行为大鼠的静态通气以及对低氧和过度易受通气反应的影响。 （ii）评估IH对运动神经长期促进（LTF）的影响。 （iii）确定信号传导途径，尤其是蛋白激酶C（PKC）的潜在作用，在IH通过发育中施加的通风的长期修饰中。因此，这项工作将有助于理解介导的潜在机制，不仅早期适应IH，而且还提供了对通风的长期变化的见解，而通气的长期变化可能会在临界阶段在成熟的临界阶段应用。